Effects of Sulpiride and Oxypertine on the Dopaminergic System in the Rat Striatum

We have examined the effects of sulpiride, oxypertine and haloperidol on the behavioral and biochemical dopamine receptor function in the rat striatum. Although acute treatment with haloperidol or oxypertine induced catalepsy, tolerance to catalepsy developed following chronic treatment with haloperidol but not with oxypertine. Rats treated with acute or chronic sulpiride did not show signs of catalepsy. Intracerebroventricular administration of sulpiride, however, induced catalepsy and tolerance developed after chronic treatment. After chronic treatment with either of these three drugs, dopamine D2 receptors were up-regulated in the striatum. While acute administration of haloperidol, sulpiride or oxypertine increased the concentration of homovanillic acid in the striatum, the rate of increases was attenuated following chronic treatment with haloperidol or sulpiride, but not with oxypertine. While acute administration of sulpiride or oxypertine decreased dopamine, the decrease was attenuated following repeated administration of sulpiride but not of oxypertine. These results suggest that the unique pharmacological profile of oxypertine may be related to its therapeutic effect of activating apathetic patients, and that both sulpiride and oxypertine may cause tardive dyskinesia, as haloperidol does.